We are studying biochemical events characteristic of malignant tumor cells, which must be highly motile while invading tissue and metastasizing to distant sites. We have found that a number of metastatic cell lines produce and respond to autocrine motility factors. A partially purified material from the conditioned media of a human melanoma cell line was found to be a protein with an Mr of about equal to 55 KD. The material induces a strong chemotactic response in the producer cells and appears to exert its action by perturbing membrane phospholipid metabolism of the cell. We have extended these observations to 3T3 cells and their transformed metastatic counterparts. We find that the transformed cells produce and respond well to autocrine factors but poorly to platelet-derived growth factor (PDGF). The nontransformed cells, on the other hand, respond well to PDGF but to a lesser exent to the autocrine factors of the transformed cells. The nontransformed cells do not produce autocrine motility factors. These results suggest that an important characteristic of the metastatic phenotype of malignant cells is their ability to produce and respond to autocrine motility factors.